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Abnormal uterine bleeding in nonpregnant

reproductive-age patients: Terminology,
evaluation, and approach to diagnosis
Author: Andrew M Kaunitz, MD
Section Editors: Robert L Barbieri, MD, Deborah Levine, MD
Deputy Editor: Alana Chakrabarti, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Dec 2022. | This topic last updated: Aug 29, 2022.

INTRODUCTION

Abnormal uterine bleeding (AUB; a term which refers to uterine bleeding of

abnormal quantity, duration, or schedule) is a common gynecologic concern in
reproductive-age females. AUB can be caused by structural uterine pathology (eg,
fibroids, endometrial polyps, adenomyosis, neoplasia) or nonuterine causes (eg,
ovulatory dysfunction, disorders of hemostasis, medications) ( table 1).

The terminology of AUB and evaluation of nonpregnant reproductive-age patients

with AUB will be reviewed here. The terminology of normal menstrual bleeding, an
overview of genital tract bleeding in female patients, and the evaluation of AUB in
other patient populations are reviewed in detail separately.

● Terminology of normal menstrual bleeding (see "Normal menstrual cycle",

section on 'Definitions of normal uterine bleeding (menstruation)')

● Causes of genital tract bleeding in female patients (see "Causes of female

genital tract bleeding")
 ● Bleeding in adolescents (see "Abnormal uterine bleeding in adolescents:
Evaluation and approach to diagnosis")

● Bleeding in perimenopausal patients (see "Clinical manifestations and

diagnosis of menopause")

● Bleeding in postmenopausal patients (see "Approach to the patient with

postmenopausal uterine bleeding")

● Bleeding in pregnant patients (see "Evaluation and differential diagnosis of

vaginal bleeding before 20 weeks of gestation")

DEFINITIONS

Standard definitions of normal and abnormal menstrual bleeding are presented in

the table ( table 2) [1].

● Abnormalities in frequency ( figure 1)

• Frequent – Frequent menstrual bleeding refers to periods that start at

intervals <24 days.

• Infrequent – Infrequent menstrual bleeding refers to periods that start at

intervals >38 days.

• Absent – Absence of menses is either primary (absence of menarche by age

15 years) or secondary (absence of spontaneous menstrual bleeding for six
months in a patient who previously had menstrual bleeding) amenorrhea;
these are discussed in detail separately. (See "Causes of primary
amenorrhea" and "Evaluation and management of primary amenorrhea"
and "Epidemiology and causes of secondary amenorrhea" and "Evaluation
and management of secondary amenorrhea".)

● Irregular bleeding ( figure 2) – The definition of irregular bleeding depends

on patient age:

• 18 to 25 years: cycle length variance >9 days

• 26 to 41 years: cycle length variance >7 days
 • 42 to 45 years: cycle length variance >9 days

For patients <18 or >45 years, the >9-day definition is also applied, although
the evidence defining normal in these groups is less clear.

● Prolonged menstrual bleeding ( figure 3) is defined as menstrual bleeding

consistently lasting >8 days; this is often, but not always, associated with heavy
menstrual bleeding (HMB).

There is no consensus on the lower limit of normal for the duration of

menstrual bleeding.

● Abnormalities in volume ( figure 4)

• Heavy – For clinical purposes, HMB is defined as a volume that interferes

with the patient's physical, social, emotional, and/or material quality of life
[1-3]. It is based on the patient's perception of increased daily or total
monthly volume of menstrual blood flow, regardless of the duration,
frequency, or regularity. It should be noted that some patients have had
HMB "normalized" by family members, friends, or health care providers,
and therefore think their heavy volume is "normal." Patient self-reports,
however, can be inaccurate indicators of the quantity of blood loss [4-9]. In
one study including over 200 patients reporting heavy periods, only one-
third of patients had objectively documented excessive bleeding (ie, >80 mL
blood loss per cycle) [10].

Direct measurement of menstrual blood loss, used in the setting of clinical

trials, requires individuals to collect all menstrual products and other blood
loss and submit these for laboratory analysis, usually via the alkaline
hematin method, which is cumbersome and expensive [9,11,12]. When
menstrual blood loss is measured directly, the definition of HMB is >80 mL
menstrual blood loss per cycle. Indirect assessment of menstrual volume
(eg, semiquantitative pictorial blood loss assessment charts) has been
developed [13,14].

• Light – Light menstrual bleeding is uncommon and rarely related to

pathology, although it may be a presenting symptom of cervical stenosis or
 intrauterine synechiae. Individuals who express concern about light periods
may perceive a heavy, red bleed as a sign of good health [15].

For research purposes, <5 mL is considered "low volume," a metric that can
only be assessed quantitatively with methods like the alkaline hematin
assay [11,16].

● Intermenstrual bleeding ( figure 5) refers to AUB that occurs between well-

defined cyclical menses. The distinction between bleeding and spotting is
based on the patient's need for menstrual product use ( table 3).
Intermenstrual bleeding can also be difficult to distinguish from irregular
and/or very frequent menses; thus, care must be taken before applying this
term to patients with these other abnormalities. (See "Causes of female genital
tract bleeding".)

Intermenstrual bleeding can be cyclical or acyclical.

• Cyclical midcycle intermenstrual bleeding – A small amount of bleeding

arising from the endometrium around midcycle occurs in approximately 9
percent of all reproductive-age females [17]. This is thought to be
associated with the midcycle drop in circulating estradiol levels that occurs
just after ovulation [18].

• Acyclical intermenstrual bleeding – Intermenstrual bleeding that is not

cyclical or predictable is typically associated with nonmalignant lesions,
such as chronic cervicitis/endometritis or polyps of the cervix or
endometrium or intracavitary uterine fibroids; postcoital bleeding is a
frequent symptom. Less commonly, such bleeding can be indicative of
pathologic process, such as cervical or endometrial cancer.

Terms not used — There is consensus that some traditional AUB terms should be
abandoned because they are confusing and/or poorly defined [19-21]. These terms
include menorrhagia, metrorrhagia, polymenorrhea, hypermenorrhea,
oligomenorrhea, and dysfunctional uterine bleeding.

ETIOLOGY
The International Federation of Gynecology and Obstetrics (FIGO) classification
system PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia,
coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified)
is reviewed in detail separately ( figure 6). (See "Causes of female genital tract
bleeding", section on 'Uterine bleeding'.)

INITIAL EVALUATION OF ALL PATIENTS

In a reproductive-age patient, a single isolated bleeding event that does not result in
hemodynamic instability and occurs in the setting of otherwise normal menstrual
cycles may not require evaluation other than asking the patient to keep a menstrual
diary. By contrast, even a single episode of any postmenopausal bleeding is
considered abnormal and requires evaluation. (See "Approach to the patient with
postmenopausal uterine bleeding", section on 'Initial evaluation'.)

Assess hemodynamic stability — Initial triage includes assessment of

hemodynamic stability since hemodynamically unstable patients (eg, tachycardic,
hypotensive, orthostatic) need to be stabilized in the emergency department before
proceeding with additional evaluation of the AUB. (See "Approach to the adult with
vaginal bleeding in the emergency department" and "Managing an episode of acute
uterine bleeding", section on 'Managing hemodynamically unstable patients'.)

Hemodynamically stable patients are typically evaluated in the outpatient setting

[22]. However, in young healthy patients, vital signs, including postural changes,
may be normal early in the course of significant bleeding due to compensatory
mechanisms [23].

History

Gynecologic and obstetric history

● Recent or current pregnancy – Pregnancy history is obtained; bleeding is

common in pregnancy (all trimesters) and after pregnancy loss or termination.
(See "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks
of gestation".)
● Menstrual history and bleeding pattern – The following questions can be
used to help elicit the patient's menstrual history and bleeding pattern:

• What was the first day of the last menstrual period and several previous
menstrual periods?

• For how many days does bleeding continue? How many days of full
bleeding and how many days of light bleeding or brown staining does this
include?

• Does bleeding occur between menstrual periods?

• If bleeding is irregular, how many bleeding episodes have there been in the
past 6 to 12 months? What is the average time from the first day of one
bleeding episode to the next?

• Is the bleeding associated with dysmenorrhea or dyspareunia (ie,

suggestive of endometriosis and/or adenomyosis)?

• How heavy is the bleeding? Questions that help to characterize the volume
of uterine bleeding are shown in the table ( table 4).

• Is the patient certain that the bleeding is from the vagina?

- Does the patient see the blood in the toilet only during or after either
urination or defecation?

- Does the patient see the bleeding only when wiping with toilet tissue?
If so, has the patient tried to separately dab the urethra, vagina, and
anus with toilet tissue to check the source of the bleeding?

- If the patient uses a pad, on what part of the pad is blood visible? If the
patient uses a tampon, is bleeding visible while a tampon is in the
vagina?

In general, if the bleeding occurs solely with urination or defecation and the
pattern of bleeding or findings on physical examination are consistent with
a urinary or gastrointestinal tract source, this should be the focus of further
evaluation. Changes in bladder or bowel function may also suggest a mass
 effect from an enlarged fibroid uterus or a neoplasm. Evaluation of
hematuria and rectal bleeding is discussed in detail separately. (See
"Etiology and evaluation of hematuria in adults" and "Approach to minimal
bright red blood per rectum in adults".)

• Were there precipitating factors, such as trauma, intercourse, or a

procedure? Bleeding related to trauma or intercourse suggests a vaginal or
cervical source of bleeding (eg, cervical dysplasia, cervicitis, vulvovaginal
atrophy, cervical polyp), while bleeding after a procedure (eg, pregnancy
termination, intrauterine device [IUD] placement) may suggest a uterine
source of bleeding. (See "Postcoital bleeding in females".)

● Sexual history – A sexual history helps to determine whether the patient

might be pregnant, as pregnancy is a common cause of uterine bleeding;
however, a pregnancy test is generally also performed. (See 'Pregnancy test'
below.)

A sexual history may also help determine the patient's risk for sexually
transmitted infections (eg, Chlamydia trachomatis, Neisseria gonorrhoeae,
trichomonas, herpes simplex), which can cause cervicitis and present with
cervical bleeding. Patients at risk for sexually transmitted infections should be
asked if they have lower abdominal pain, fever, and/or vaginal discharge, all
which suggest pelvic infection (eg, pelvic inflammatory disease [PID],
endometritis). In one series, 15 percent of participants with upper genital tract
infection presented with AUB [24]. (See "Clinical manifestations and diagnosis
of Chlamydia trachomatis infections" and "Clinical manifestations and
diagnosis of Neisseria gonorrhoeae infection in adults and adolescents" and
"Acute cervicitis" and "Endometritis unrelated to pregnancy" and "Pelvic
inflammatory disease: Clinical manifestations and diagnosis".)

● History of obstetric or gynecologic surgery – A history of obstetric or

gynecologic surgery may suggest an underlying disorder that can be
associated with AUB:

• A prior cesarean birth can result in a cesarean scar defect (particularly if a

patient has had multiple cesarean births)
 • Past myomectomy suggests the possibility of recurrent or persistent
uterine fibroids

• Past excisional cervical procedures performed for diagnosis or

management of cervical intraepithelial neoplasia suggest the possibility of
recurrent or persistent cervical neoplasia

• Rarely, uterine surgery can result in an arteriovenous malformation (AVM);

enhanced myometrial vascularity (EMV) is a distinct entity and occurs in the
setting of pregnancy and retained products of conception.

These entities are discussed in more detail below. (See 'Intermenstrual

bleeding' below and 'Heavy menstrual bleeding' below.)

● Contraceptive history – Many contraceptives can cause AUB; the pattern

varies depending on the specific contraceptive. Patients using combined
estrogen-progestin contraceptives or progestin-only contraceptives may
develop unscheduled bleeding, decreased menstrual flow, or amenorrhea. The
copper IUD increases menstrual flow while some types of levonorgestrel IUDs
(eg, LNG 52; Mirena, Liletta) are associated with decreased menstrual flow and
amenorrhea. (See 'Secondary evaluation' below and "Evaluation and
management of unscheduled bleeding in individuals using hormonal
contraception".)

● Risk factors for endometrial cancer – Endometrial hyperplasia and

carcinoma often present with AUB ( table 5). (See 'Based on risk factors for
endometrial cancer' below and 'Endometrial sampling: Choice of modality'
below.)

Medical history — The review of systems and medical history may reveal a

condition or medication associated with AUB. Patients should be asked about a
family history of bleeding disorders, thyroid disease, and hyperprolactinemia. They
also should be asked about associated symptoms including bruising or petechiae,
galactorrhea, heat or cold intolerance, and about symptoms suggestive of
hypothalamic dysfunction (eg, recent illness, stress, excessive exercise, eating
disorder).
● Medications that can cause AUB include anticoagulants, which may result in
heavy or prolonged uterine bleeding, and medications that cause
hyperprolactinemia, which can result in oligomenorrhea or amenorrhea
( table 6). (See 'Secondary evaluation' below.)

● Bleeding disorders – Bleeding disorders may present at menarche or later

during a patient's reproductive years. The prevalence of von Willebrand
disease (an inherited bleeding disorder), which is approximately 1 percent in
the general population, is substantially higher among patients with chronic
heavy uterine bleeding [25]. Other bleeding disorders associated with heavy
menstrual bleeding (HMB) include immune thrombocytopenia, platelet
function defect, or an acquired bleeding diathesis (eg, hematologic
malignancy, liver or renal disease, prescription or nonprescription drugs)
( table 7) [25-31]. (See "Causes of female genital tract bleeding", section on
'Coagulopathy (AUB-C)' and "Approach to the adult with a suspected bleeding
disorder", section on 'Patient history' and "Clinical presentation and diagnosis
of von Willebrand disease", section on 'Changes with aging and pregnancy'.)

Indications for coagulation testing are discussed below. (See 'Heavy menstrual
bleeding' below.)

● Endocrine disorders – Thyroid disease is often associated with

oligomenorrhea or amenorrhea; although traditionally thought to be a
common cause of HMB, available data suggest that it is an uncommon etiology
of this bleeding pattern [32,33]. (See "Clinical manifestations of
hypothyroidism", section on 'Reproductive abnormalities'.)

Hyperprolactinemia is also associated with amenorrhea. (See 'Heavy menstrual

bleeding' below and 'Based on bleeding pattern' below.)

● Other – Patients with chronic medical conditions (eg, type 1 diabetes mellitus,
celiac disease, chronic kidney disease [34-37]) may develop secondary
amenorrhea when it is severe enough to result in a decrease in hypothalamic
gonadotropin-releasing hormone (GnRH) secretion and/or when it is
associated with nutritional deficiencies. (See 'Amenorrhea' below and
"Epidemiology and causes of secondary amenorrhea", section on 'Systemic
 illness'.)

Physical examination — The goal of the physical examination is to look for signs of

systemic illness, such as fever, ecchymoses, an enlarged thyroid gland, or evidence
of hyperandrogenism (eg, hirsutism, acne, clitoromegaly, male pattern balding).
Acanthosis nigricans may be seen in patients with polycystic ovary syndrome
(PCOS). Galactorrhea (bilateral milky nipple discharge unrelated to pregnancy or
breastfeeding) suggests the presence of hyperprolactinemia.

A complete pelvic examination should be performed, with a particular focus on:

● Potential sites of bleeding from the vulva, vagina, cervix, urethra, anus, or
perineum ( table 1). Any abnormal finding should be noted (eg, mass,
laceration, ulceration, friable area, vaginal or cervical discharge, foreign body,
urethral caruncle, hemorrhoid) as possible evidence of a nonuterine source of
bleeding.

● Current uterine bleeding – The presence and volume of bleeding from the
cervical os and blood or blood clots in the vaginal vault should be noted.

● Size and contour of the uterus – An enlarged uterus may be due to pregnancy,
uterine leiomyomas, adenomyosis, or uterine malignancy. Limited uterine
mobility should be noted, if present; this finding suggests that pelvic
adhesions (from prior infection, surgery, or endometriosis) or a pelvic mass is
present. A boggy, globular, tender uterus may be noted in patients with
adenomyosis. Uterine tenderness is often present in patients with PID but is
not consistently found in those with chronic endometritis. (See "Uterine
adenomyosis", section on 'Pelvic examination' and "Endometriosis: Clinical
features, evaluation, and diagnosis", section on 'Physical examination' and
"Endometritis unrelated to pregnancy", section on 'Clinical manifestations and
diagnosis'.)

● Presence of an adnexal mass or tenderness – This may reflect a tubo-ovarian

abscess which may be associated with endometritis. Rarely, an ovarian
neoplasm (eg, granulosa cell tumor) may be hormonally active and cause
endometrial neoplasia.
Pregnancy test — Pregnancy should be excluded in all reproductive-age patients
with AUB. Pregnancy testing should be performed even in patients with recent
vaginal bleeding since this may represent bleeding during pregnancy rather than
menses. It should also be performed in patients who report no sexual activity and in
those who report use of contraception.

A urine human chorionic gonadotropin (hCG) test may be performed as an initial

test in a clinic or urgent care setting since these results are available quickly.

● If the urine test is negative but the clinician continues to suspect early
pregnancy may be present, serum hCG should be measured. A serum hCG
assay can detect a pregnancy by one week after conception compared with
only 50 percent of urine hCG tests by 11 days (and 98 percent by 14 days) [38-
40].

● If either the urine or serum test is positive, patients should be evaluated for
pregnancy-related causes of bleeding. Serial quantitative serum hCG testing is
appropriate if ectopic pregnancy or spontaneous abortion is suspected.
Gestational trophoblastic disease, which in some cases presents weeks to
years after a pregnancy, is also associated with AUB and a positive pregnancy
test. (See "Evaluation and differential diagnosis of vaginal bleeding before 20
weeks of gestation" and "Hydatidiform mole: Epidemiology, clinical features,
and diagnosis".)

Diagnosis of pregnancy is discussed in detail separately. (See "Clinical

manifestations and diagnosis of early pregnancy".)

Role of ultrasound — While many patients will ultimately need an ultrasound as

part of the secondary evaluation, we typically avoid routinely ordering it as part of
the initial evaluation in all patients. (See 'Secondary evaluation' below.)

SECONDARY EVALUATION

Additional evaluation is selective and depends on information obtained during the

history and physical examination ( table 8). (See 'History' above and 'Physical
examination' above.)
Based on bleeding pattern

Heavy menstrual bleeding — Based on current terminology, heavy menstrual

bleeding (HMB; regular bleeding that is heavy or prolonged) refers only to cyclic
(ovulatory) menses [41]. (See 'Definitions' above.)

Further testing is guided by findings on history and physical examination

( table 9). Patients with a TCu-380A (ParaGard) intrauterine device (IUD) may have
iatrogenic HMB and not require further evaluation; this is discussed in detail
separately. (See "Intrauterine contraception: Management of side effects and
complications", section on 'Continued bleeding and cramping'.)

● Imaging is typically performed to assess for the following (see 'Imaging:

Choice of modality' below):

• Uterine fibroids (an enlarged uterus or discrete mass may be palpated on

examination); HMB associated with uterine leiomyomas is most likely to
occur with submucosal leiomyomas, but leiomyomas at other sites may
also cause AUB. (See "Uterine fibroids (leiomyomas): Epidemiology, clinical
features, diagnosis, and natural history".)

• Adenomyosis (a boggy uterus may be palpated on examination or the

patient may report a history of dysmenorrhea). (See "Uterine
adenomyosis".)

• Endometrial polyps (in the absence of a prolapsed polyp, physical

examination is usually normal). (See "Endometrial polyps".)

• Uterine arteriovenous malformation (AVM; a rare cause of HMB that should

be suspected when an invasive procedure [eg, dilation and curettage in a
nonpregnant patient] for unexplained bleeding aggravates the bleeding).
AVM represents a distinct entity from enhanced myometrial vascularity
(EMV), which is associated with retained products of conception and occurs
postpartum or after pregnancy loss/termination [42,43]. (See "Causes of
female genital tract bleeding", section on 'Not otherwise classified (AUB-
N)'.)

● Laboratory tests – A complete blood count is performed for all patients with
 HMB to assess for anemia; assessing a ferritin level can identify patients who,
although not currently anemic, have depleted iron stores. (See "Causes and
diagnosis of iron deficiency and iron deficiency anemia in adults", section on
'Diagnostic evaluation'.)

An elevated white blood cell count may suggest an infection (eg, pelvic
inflammatory disease [PID], acute endometritis after a gynecologic procedure)
or, uncommonly, leukemia as a cause of HMB [31]. By contrast, the white blood
cell count is typically normal in chronic endometritis. (See "Endometritis
unrelated to pregnancy" and "Pelvic inflammatory disease: Clinical
manifestations and diagnosis", section on 'Point-of-care and laboratory tests'.)

Additional laboratories are typically performed for patients with HMB and
concerns for any of the following:

• Bleeding disorder – Patients with symptoms, risk factors (eg, anticoagulant

therapy, thrombocytopenia, liver or renal disease), or a family history of a
bleeding disorder require further evaluation. This is discussed separately.
(See "Approach to the adult with a suspected bleeding disorder", section on
'Laboratory evaluation'.)

Patients who are taking warfarin should have coagulation parameters (eg,
international normalized ratio [INR]) assessed to see if the effect is within
the therapeutic window. (See "Approach to the adult with a suspected
bleeding disorder", section on 'Medication use'.)

• Thyroid disease – A serum thyroid-stimulating hormone (TSH) level should

be performed if thyroid disease is suspected. (See "Diagnosis of and
screening for hypothyroidism in nonpregnant adults" and "Diagnosis of and
screening for hypothyroidism in nonpregnant adults", section on
'Diagnosis'.)

● Endometrial sampling is typically performed for select patients with HMB

with risk factors, or suspicion, for uterine malignancy ( table 5 and
table 10) (see 'Based on risk factors for endometrial cancer' below and
'Endometrial sampling: Choice of modality' below). Endometrial hyperplasia or
carcinoma or, rarely, uterine sarcoma may be associated with HMB, but the
 typical bleeding pattern for these conditions is postmenopausal bleeding. (See
"Endometrial sampling procedures", section on 'Indications'.)

Intermenstrual bleeding — Intermenstrual uterine bleeding may be related to a

variety of etiologies, including abnormalities of the cervix (eg, cervical polyps,
cervicitis, ectropion, cervical cancer), uterus (eg, chronic endometritis, endometrial
polyps), or unscheduled bleeding due to a contraceptive method. These conditions
are discussed separately. (See "Causes of female genital tract bleeding".)

Further testing is guided by findings on history and physical examination

( table 11).

● Imaging is typically performed for patients with intermenstrual bleeding to

assess for the following (see 'Imaging: Choice of modality' below):

• Endometrial polyps (in the absence of a prolapsed polyp, physical

examination is usually normal). (See "Endometrial polyps".)

• Cesarean scar defect. Approximately two-thirds of patients who have had

one or (in particular) multiple cesarean births may have a cesarean scar
defect, and approximately one-third of patients with this condition
experience cyclical, postmenstrual bleeding [44]. The mechanism by which
this occurs is discussed in detail separately.

● Endometrial sampling is typically performed for patients with intermenstrual

bleeding and concerns for uterine malignancy ( table 5 and table 10). (See
'Based on risk factors for endometrial cancer' below and 'Endometrial
sampling: Choice of modality' below.)

Endometrial sampling may also be performed in patients with intermenstrual

bleeding in whom chronic endometritis is suspected. (See 'History' above.)

● Laboratory tests are generally not required for patients with intermenstrual
bleeding.

Irregular bleeding — Irregular uterine bleeding is most commonly associated

with ovulatory dysfunction (AUB-O) ( table 12) and typically occurs at the extremes
of reproductive age (ie, postmenarchal, perimenopausal) (see 'Definitions' above).
Patients may either have anovulation or oligo-ovulation, in which they shift between
ovulatory cycles and anovulation. Bleeding is typically characterized by phases of no
bleeding that may last for two or more months and other phases with either
spotting or episodes of heavy bleeding. Molimina symptoms (eg, breast tenderness,
bloating, fatigue) are typically absent.

While further evaluation is not generally required to confirm ovulatory dysfunction,

it is helpful in identifying the cause of bleeding so that it can be treated, and adverse
consequences can be prevented. Further evaluation may include:

● Laboratory tests

• Thyroid function tests – A TSH level should be measured to exclude thyroid

disease as a cause of anovulation. (See 'Heavy menstrual bleeding' above.)

• Prolactin level – A prolactin level should be measured in patients who

complain of anovulatory bleeding, amenorrhea, or galactorrhea, or are
taking medications that can cause hyperprolactinemia ( table 6). (See
"Clinical manifestations and evaluation of hyperprolactinemia".)

• Androgen levels – Serum androgens should be measured in patients with

irregular bleeding and signs of androgen excess. Hirsutism (excessive male-
pattern facial and body hair) is far more common than virilization
(deepening of the voice, temporal balding, breast atrophy, changes toward
a male body habitus, and/or clitoromegaly) [45]. Polycystic ovarian
syndrome (PCOS) is the most common cause of hirsutism and amenorrhea
or anovulatory bleeding. However, clinical manifestations of
hyperandrogenism may also be seen in patients with congenital adrenal
hyperplasia. If virilization is present, a more severe androgen excess should
be suspected and the patient should be evaluated for an androgen-
secreting tumor of the adrenal gland or ovary. (See "Pathophysiology and
causes of hirsutism".)

• Follicle-stimulating hormone (FSH) or luteinizing hormone (LH) – FSH and

LH are released by the pituitary gland. If premature ovarian insufficiency is
suspected, a serum FSH should be performed. For patients with suspected
hypothalamic dysfunction (due to poor nutrition or intense exercise), FSH,
 LH, and estradiol should be assessed. (See "Clinical manifestations and
diagnosis of primary ovarian insufficiency (premature ovarian failure)",
section on 'Diagnosis'.)

• Estrogen levels – As with FSH, if premature ovarian insufficiency is

suspected, a serum estradiol assessment should be performed. Estrogen
excess due to an estrogen-secreting ovarian tumor is a rare etiology of AUB
but should be considered if an adnexal mass is present and if other
etiologies have been excluded. (See "Sex cord-stromal tumors of the ovary:
Epidemiology, clinical features, and diagnosis in adults".)

● Endometrial sampling is typically performed for patients with irregular

bleeding that has been present for six months or more given their increased
risk of endometrial hyperplasia/neoplasia ( table 5 and table 10). This is
discussed in more detail below. (See 'Based on risk factors for endometrial
cancer' below and 'Endometrial sampling: Choice of modality' below.)

● Imaging – Imaging is generally not required for patients with irregular

bleeding due to ovulatory dysfunction. This is discussed in detail separately.
(See "Diagnosis of polycystic ovary syndrome in adults", section on
'Transvaginal ultrasound'.)

Amenorrhea — Amenorrhea refers to absence of bleeding for at least three usual

cycle lengths. Amenorrhea may be primary (ie, menarche is absent) or secondary (ie,
menses cease after menarche). The evaluation of amenorrhea is discussed
separately. (See "Evaluation and management of primary amenorrhea" and
"Evaluation and management of secondary amenorrhea".)

Decreased volume — Patients sometimes report periods that are regular but have
become unusually light or of short duration. Patients using hormonal contraception
(including levonorgestrel IUD) often will experience decreased menstrual blood loss;
this is expected and does not require further evaluation. (See "Combined estrogen-
progestin oral contraceptives: Patient selection, counseling, and use", section on
'Advantages'.)

Causes of decreased menstrual volume that do require further evaluation include

partial cervical stenosis or Asherman syndrome; these are discussed separately. (See
"Intrauterine adhesions: Clinical manifestation and diagnosis".)

Regular menses with increased frequency — During the menopausal transition,

patients may experience a decrease in the interval between menses. Cycle length
that has shortened, but not to less than every 24 days, may be normal during this
phase. If the bleeding is also irregular, heavy, or occurs less often than every 24
days, other etiologies should be investigated. (See 'Irregular bleeding' above and
'Heavy menstrual bleeding' above.)

Based on risk factors for endometrial cancer — Patients with AUB and obesity or
other risk factors for endometrial cancer ( table 5) should be evaluated with
endometrial sampling.

Indications for endometrial sampling in patients of reproductive age with AUB vary
by age group ( table 10):

● Age 45 years to menopause – Bleeding that is frequent, heavy, prolonged, or

occurs between cycles (ie, intermenstrual bleeding) ( table 2).

● Age <45 years – Bleeding that is persistent (usually defined as six months or
more [46]) and occurs in the setting of one of the following: a history of
unopposed estrogen exposure (eg, obesity, chronic ovulatory dysfunction)
[47,48], failed medical management of the bleeding, or in patients at high risk
of endometrial cancer (eg, tamoxifen therapy, Lynch or Cowden syndrome).

Use of 45 years old as the threshold for increased concern regarding

endometrial neoplasia is supported by evidence that the risk of endometrial
hyperplasia and carcinoma increases with advancing age: 0.05, 6, and 19
percent of cases of endometrial cancer occur in patients ages 15 to 19, 25 to
44, and 45 to 54 years, respectively [49-52]. This age threshold is also
consistent with American College of Obstetricians and Gynecologists (ACOG)
guidelines [47,53]. (See "Endometrial hyperplasia: Clinical features, diagnosis,
and differential diagnosis", section on 'Epidemiology' and "Endometrial
carcinoma: Epidemiology, risk factors, and prevention", section on
'Epidemiology'.)

Patients with obesity and AUB are at an increased risk of endometrial neoplasia
regardless of age. This is because patients with obesity have high levels of
endogenous estrogen due to the conversion of androstenedione to estrone and the
aromatization of androgens to estradiol in adipose tissue, and this becomes a
source of endogenous unopposed estrogen in the setting of ovulatory dysfunction.
In one retrospective study including over 900 premenopausal patients with AUB
(average age 42 to 44 years), those with a body mass index ≥30 kg/m2 were fourfold
more likely to develop complex endometrial hyperplasia (with or without atypia) or
endometrial carcinoma than other patients [54]. (See "Endometrial carcinoma:
Epidemiology, risk factors, and prevention", section on 'Obesity'.)

SUBSEQUENT EVALUATION FOR SELECT PATIENTS

In patients with AUB in whom the initial and secondary evaluation are normal,
hormonal therapy (eg, combination estrogen-progestin contraceptives,
levonorgestrel intrauterine device [IUD]) is often used as initial empiric treatment.
(See "Abnormal uterine bleeding in nonpregnant reproductive-age patients:
Management", section on 'Preferred approach for most patients'.)

In addition, the possibility of concurrent factors should also be considered. For

example, patients with uterine fibroids or adenomyosis may not present for care
until anovulation associated with perimenopause causes heavy, irregular bleeding; a
patient with a fibroid uterus may also have a defect of hemostasis that is the
primary reason for the heavy bleeding; a patient with a fibroid uterus may
experience bleeding from an endometrial or endocervical malignancy unrelated to
the fibroid itself. Therefore, several potential etiologies often need to be
investigated and, if a cause of AUB is determined but bleeding persists despite
treatment, the patient should be evaluated for additional etiologies.

SPECIAL CONSIDERATIONS

Endometrial sampling: Choice of modality — Endometrial sampling is typically

performed as an office biopsy, but dilation and curettage or hysteroscopically-
directed biopsy may be performed if bleeding persists after a normal endometrial
biopsy or if there are other indications for an operative procedure. (See
"Endometrial sampling procedures" and "Overview of the evaluation of the
endometrium for malignant or premalignant disease".)

While transvaginal ultrasound can provide useful information regarding structural

causes of AUB (eg, fibroids, adenomyosis, polyps), measurement of endometrial
thickness is not used as an alternative to endometrial sampling for the evaluation of
endometrial neoplasia in reproductive-age patients as major variation in
endometrial thickness occurs during the normal menstrual cycle. (See "Overview of
the evaluation of the endometrium for malignant or premalignant disease", section
on 'Premenopausal patients with abnormal bleeding'.)

Imaging: Choice of modality — The choice of pelvic imaging is based on the

clinician's judgment, depending on patient age, history, and symptoms.

● Pelvic ultrasound – Pelvic ultrasound is the first-line imaging study in patients

with AUB. Transvaginal examination should be performed, unless there is a
reason to not perform the vaginal study (eg, patient declines). Transabdominal
sonography should also be performed if transvaginal imaging does not allow
adequate assessment of the uterus or adnexa or if a large pelvic mass is
present.

Ultrasound is effective at characterizing anatomic as well as vascular uterine

pathology and adnexal lesions [55]. As noted above, assessment of
endometrial thickness is often not useful in premenopausal patients. (See
'Endometrial sampling: Choice of modality' above.)

● If intracavitary pathology (lesions that protrude into the uterine cavity [ie,
endometrial polyps, submucosal myomas, intramural myomas with an
intracavitary component]) is suspected based upon the initial ultrasound, the
patient may be evaluated with either saline infusion sonohysterography or
hysteroscopy.

• Saline infusion sonography (SIS) – SIS (also called sonohysterography) is a

technique in which sterile saline is instilled into the endometrial cavity and
a transvaginal ultrasound examination is performed [56]. This procedure
allows for an architectural evaluation of the uterine cavity to detect lesions
(eg, polyps or small submucous fibroids) that may be missed or poorly
 defined by transvaginal sonography alone ( image 1). SIS is also useful in
evaluating AUB associated with cesarean scar defects [57]. (See "Saline
infusion sonohysterography".)

• Hysteroscopy – Hysteroscopy provides direct visualization of the

endometrial cavity. Diagnostic hysteroscopy can be performed in an office
setting. In an operative setting, hysteroscopy allows targeted biopsy or
excision of lesions identified during the procedure [58,59]. (See "Overview
of hysteroscopy".)

We suggest SIS for most patients for intracavitary evaluation. Both SIS and
hysteroscopy are effective tests for diagnosing endometrial polyps and
submucosal leiomyoma [60], while ultrasound alone has limited sensitivity and
specificity for the characterization of these lesions [61,62]. Compared with
hysteroscopy, the major advantage of SIS is that it can assess the depth of
extension of leiomyomas into the myometrium or serosal surface ( image 2).
Some fibroids appear to be submucosal at hysteroscopy but are actually
intramural with a component that protrudes into the uterine cavity. This
information and the ability to identify fibroids at other sites ( figure 7 and
figure 8) can help surgical planning. Some data also suggest that SIS is less
painful than office hysteroscopy [61,63]. SIS also is able to identify asymmetric
or focal endometrial thickening, a potentially important marker of endometrial
neoplasia ( image 3) [60].

Advantages of hysteroscopy are that office hysteroscopy may offer patients

greater convenience, particularly if it can be performed at the same visit as the
initial evaluation. Operative hysteroscopy, including resection of endometrial
polyps or submucosal fibroids, is not typically available in an office setting and
therefore, in most settings, is not part of the initial evaluation of AUB in the
United States.

Factors such as convenience, availability of equipment and trained personnel,

and cost of SIS and hysteroscopy vary in different clinical settings, and these
factors often influence the choice of study. Of note, the United Kingdom
National Institute for Health and Care Excellence (NICE) guidelines regarding
heavy menstrual bleeding (HMB) suggest that for patients with AUB and
 suspected submucosal fibroids, polyps or endometrial pathology outpatient
hysteroscopy be performed as initial evaluation [64].

● Other – Magnetic resonance imaging (MRI) should be used for pelvic

assessment only as a follow-up imaging test when additional information (eg,
further characterization of a lesion) that is not available on ultrasound could
potentially impact clinical management.

Computed tomography (CT) has no role in routine pelvic assessment of AUB.

(See "Overview of the evaluation of the endometrium for malignant or
premalignant disease", section on 'Other'.)

WHEN TO REFER

Referral to a gynecologist is appropriate for patients who have heavy bleeding,

severe anemia, persistent bleeding despite treatment, if there is suspicion of
malignancy, or if surgery is required. Referral to a gynecologist is also appropriate if
the primary care clinician is not comfortable performing endometrial sampling or
placing an intrauterine device (IUD; for treatment of AUB).

If gynecologic malignancy is suspected, or if a patient with AUB would like to

conceive, referral to a gynecologic oncologist or a reproductive endocrinologist and
infertility specialist may be appropriate. In addition, if saline infusion sonography
(SIS) or hysteroscopy is indicated and the initial clinician lacks the experience or
resources to perform these procedures, referral to a gynecologist with the needed
experience and equipment is appropriate.

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links:
Abnormal uterine bleeding" and "Society guideline links: Hemophilia A and B".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond
the Basics." The Basics patient education pieces are written in plain language, at the
5th to 6th grade reading level, and they answer the four or five key questions a
patient might have about a given condition. These articles are best for patients who
want a general overview and who prefer short, easy-to-read materials. Beyond the
Basics patient education pieces are longer, more sophisticated, and more detailed.
These articles are written at the 10th to 12th grade reading level and are best for
patients who want in-depth information and are comfortable with some medical
jargon.

Here are the patient education articles that are relevant to this topic. We encourage
you to print or e-mail these topics to your patients. (You can also locate patient
education articles on a variety of subjects by searching on "patient info" and the
keyword(s) of interest.)

● Basics topics (see "Patient education: Heavy periods (The Basics)")

● Beyond the Basics topics (see "Patient education: Abnormal uterine bleeding
(Beyond the Basics)" and "Patient education: Heavy or prolonged menstrual
bleeding (menorrhagia) (Beyond the Basics)" and "Patient education: Absent or
irregular periods (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

● Definitions and etiology

• Standard definitions of abnormal menstrual bleeding (AUB) are presented

in the table ( table 2). (See 'Definitions' above.)

• Causes of AUB include structural uterine pathology (eg, fibroids,

endometrial polyps, adenomyosis, neoplasia), infections (eg, endometritis),
or nonuterine causes (eg, ovulatory dysfunction, disorders of hemostasis,
medications) ( table 1 and figure 6). (See 'Etiology' above and "Causes
of female genital tract bleeding", section on 'Uterine bleeding'.)

● Initial evaluation of all patients – All patients with AUB should have a
 complete history and physical examination. Information should be obtained on
the frequency, duration, and volume of AUB, as well as the presence of
associated symptoms and precipitating factors. Pregnancy should be excluded
in all patients. Patients with acute bleeding should be evaluated in the
emergency department. (See 'Initial evaluation of all patients' above.)

● Secondary evaluation – Further evaluation is determined by the pattern,

severity, and etiology of the bleeding ( table 8). (See 'Secondary evaluation'
above.)

• HMB – Patients with heavy menstrual bleeding (HMB) often undergo pelvic
imaging to assess for structural lesions (eg, uterine fibroid, adenomyosis,
endometrial polyp), a complete blood count (to assess for anemia,
thrombocytopenia), and measurement of ferritin level (to assess iron
stores). Additional laboratories are ordered if a bleeding disorder (eg, von
Willebrand disease) or endocrine disorder (eg, hypothyroidism) is
suspected. Endometrial sampling is performed for patients with obesity or
other risk factors for endometrial hyperplasia or carcinoma. (See 'Heavy
menstrual bleeding' above.)

• Intermenstrual bleeding – Patients with intermenstrual bleeding also

often undergo pelvic imaging (to assess for an endometrial polyp or
cesarean scar defect) and endometrial sampling (to assess for malignancy
or endometritis). (See 'Intermenstrual bleeding' above.)

• Irregular bleeding – Patients with irregular bleeding often have ovulatory

dysfunction. Laboratories may be ordered to evaluate for thyroid disease,
hyperprolactinemia, or premature ovarian insufficiency. Endometrial
sampling should be performed for persistent symptoms (six months or
more) given the increased risk of endometrial hyperplasia/neoplasia. (See
'Irregular bleeding' above.)

• Indications for endometrial sampling – Endometrial sampling should be

performed in nonpregnant patients with any bleeding pattern if obesity or
other risk factors for endometrial hyperplasia or cancer are present.
Indications for endometrial sampling vary by age group ( table 5 and
 table 10). (See 'Based on risk factors for endometrial cancer' above.)

● Causes of iatrogenic bleeding – Many contraceptives (eg, combined oral

contraceptives, intrauterine device [IUD; both hormonal and nonhormonal
types]) can cause iatrogenic AUB, which in this setting may not require further
evaluation. (See 'History' above.)

● Imaging – Pelvic ultrasound (typically transvaginal) is the first-line imaging

study in most patients. Ultrasound may be combined with either saline
infusion sonography (SIS) or hysteroscopy to provide information about lesions
that protrude into the endometrial cavity (eg, endometrial polyps, submucosal
myomas, intramural myomas with an intracavitary component). (See 'Imaging:
Choice of modality' above.)

ACKNOWLEDGMENT

The UpToDate editorial staff acknowledges Annekathryn Goodman, MD, MPH, MS,
who contributed to earlier versions of this topic review.

Use of UpToDate is subject to the Terms of Use.

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Topic 3263 Version 52.0
GRAPHICS

Causes of abnormal genital tract bleeding in females

Genital tract disorders Trauma

Uterus Sexual intercourse

Benign conditions: Sexual abuse

Endometrial polyps Foreign bodies (including intrauterine

device)
Endometrial hyperplasia
Pelvic trauma (eg, motor vehicle
Adenomyosis
accident)
Leiomyomas (fibroids)
Straddle injuries
Arteriovenous malformation (also
Cesarean scar defect (prior cesarean
referred to as enhanced
delivery)
myometrial vascularity)

Cancer:
Drugs
Contraception:
Endometrial adenocarcinoma

Sarcoma Hormonal contraceptives

Infection: Intrauterine devices

Pelvic inflammatory disease Postmenopausal hormone therapy

Endometritis Anticoagulants

Ovulatory dysfunction Tamoxifen

Corticosteroids
Cervix
Chemotherapy
Benign conditions:
Phenytoin
Cervical polyps
Antipsychotic drugs
Ectropion
Antibiotics (eg, due to toxic epidermal
Endometriosis
necrolysis or Stevens-Johnson
Cancer: syndrome)
Invasive carcinoma

Metastatic (uterus, Systemic disease

choriocarcinoma) Diseases involving the vulva:
Infection: Crohn disease
 Cervicitis Behçet syndrome

Vulva Pemphigoid

Benign conditions: Pemphigus

Skin tags Erosive lichen planus

Sebaceous cysts Lymphoma

Condylomata Bleeding disorders:

Angiokeratoma von Willebrand disease

Cancer Thrombocytopenia or platelet

dysfunction
Vagina
Acute leukemia
Benign conditions:
Some coagulation factor
Gartner duct cysts deficiencies
Polyps Advanced liver disease
Adenosis (aberrant glandular Thyroid disease
tissue)
Polycystic ovary syndrome
Cancer
Cushing syndrome
Vaginitis/infection:
Hormone-secreting adrenal and
Bacterial vaginosis ovarian tumors
Sexually transmitted infections Renal disease
Atrophic vaginitis Emotional or physical stress
Upper genital tract disease Smoking
Pelvic inflammatory disease Excessive exercise
Fallopian tube cancer
Diseases not affecting the genital
Ovarian cancer
tract
Pregnancy complications
Urethritis

Bladder cancer

Urinary tract infection

Colorectal cancer

Inflammatory bowel disease

Hemorrhoids

Other
 Endometriosis

Graphic 74527 Version 13.0

Normal menstruation parameters

Parameter Normal Abnormal

Frequency ≥24 and ≤38 days Absent (no bleeding):

amenorrhea

Frequent (<24 days)

Infrequent (>38 days)

Duration ≤8 days Prolonged (>8 days)

Regularity Regular: shortest to longest Irregular: shortest to

cycle variation: ≤7 to 9 longest cycle variation: ≥10
days* days

Flow volume (patient Patient considers normal Patient considers light

determined)
Patient considers heavy

Intermenstrual bleeding None Random

(bleeding between cyclically
Cyclic (predictable):
regular onset of menses)
Early cycle
Mid cycle
Late cycle

Unscheduled bleeding on Not applicable for patients Present

progestin±estrogen not on gonadal steroid
gonadal steroids medication
(contraceptive pills, rings,
None (for patients on
patches, IUDs, or
gonadal steroid
injections)
medication)

IUDs: intrauterine contraceptive devices.

* Normal variation depends on age; these data are calculated excluding short and long
outliers.

Data from:
1. Fraser IS, Critchley HO, Munro MG, Broder M. A process designed to lead to international agreement
on terminologies and definitions used to describe abnormalities of menstrual bleeding. Fertil Steril
2007; 87:466.
2. Fraser IS, Critchley HO, Munro MG, Broder M. Can we achieve international agreement on
terminologies and definitions used to describe abnormalities of menstrual bleeding? Hum Reprod
2007; 22:635.
 3. Fraser IS, Munro MG, Broder M, Critchley HO. International recommendations on terminologies and
definitions for normal and abnormal uterine bleeding. Semin Reprod Med 2011.

Graphic 103238 Version 5.0

Frequency of menses

The normal frequency of onset of menstrual periods is from 24 to 38 days, based on large databases
and using the 5 th to the 95 th percentiles.
(A) The top panel demonstrates an individual with a 27-day cycle that is "normal."
(B) The middle panel is a cycle length of 44 days, outside the normal range (infrequent).
(C) The bottom panel depicts a cycle length of 22 days and is, therefore, defined as being "frequent."

Reproduced with permission from Malcolm G Munro, MD, FRCSC, FACOG.

Graphic 109656 Version 4.0

Regularity of menses

Regular and irregular frequency of menses. "Regular" means "cyclically predictable" and
generally reflects the presence of consistently predictable ovulation, typically about 14 days prior
to the onset of menses.
(A) The top panel depicts a 65-day interval where the first cycle length is 29 days and the second
is 31 days, with each menstrual period lasting 5 days and day 2 having the heaviest volume. This
variation of 2 days is well within the definition of regularity: cycle length from first day of one
period to the next is fairly consistent, with each cycle length within 4 days of the others.
(B) The bottom panel demonstrates an irregular cycle, with the first cycle a length of 13 days and
a second cycle of 39 days. This variation in cycle length is outside the normal range for any age
and suggests that the patient is not ovulating regularly or not ovulating at all. Note the
variable duration and flow of the menses, also consistent with some ovulatory disorders, but not
necessary for defining "irregular" onset of menses.

Reproduced with permission from Malcolm G Munro, MD, FRCSC, FACOG.

Graphic 109657 Version 3.0
Duration of menses

The panel above demonstrates the two definitions of duration of menses. When a menstrual
period is present and lasts up to 8 days, it is considered "normal." If it is in excess of 8 days,
regardless of volume, as depicted in the center and right cluster, it is deemed "prolonged."

Reproduced with permission from Malcolm G Munro, MD, FRCSC, FACOG.

Graphic 109658 Version 3.0

Volume of menses

The volume of a menstrual period comprises the total amount of red cells, serum, transudate, and
tissue discharged from the uterus. The menstrual volume can be quantified with research
laboratory techniques, but for clinical purposes, the patient's perception of volume is of primary
importance. Each of the clusters in the above panel represents a menstrual period. The first
cluster would likely reflect the patient's perception of "normal" volume with a normal period
length of 7 days. The second cluster reflects increased volume, primarily because of prolongation
of the duration of the period: there is no increase in flow rate per day. The third cluster depicts
increased volume, but with a period of normal duration with increase in daily flow rate responsible
for the increased volume. The fourth cluster demonstrates a period with both increased duration
and increased flow rate contributing to the increase in perceived volume.

Reproduced with permission from Malcolm G Munro, MD, FRCSC, FACOG.

Graphic 109659 Version 3.0

Intermenstrual bleeding

This depicts an individual with intermenstrual bleeding. They have three periods in this
interval – the first period starts day 1, the next period starts 29 days later, and the next 30
days after that. The lighter intermenstrual bleeding is depicted as being on day 13 of the first
cycle, and on day 25 of the second. This type of random bleeding is typically seen with a focal
lesion or inflammation, including: cervicitis, cervical or endometrial polyp, or cervical cancer.

Reproduced with permission from Malcolm G Munro, MD, FRCSC, FACOG.

Graphic 109660 Version 4.0

Uterine bleeding patterns

Bleeding pattern Definition

Bleeding Any bloody vaginal discharge that requires the use of

such protection as pads or tampons

Spotting Any bloody vaginal discharge that is not large enough to

require sanitary protection

Bleeding/spotting One or more consecutive days on which bleeding or

episode spotting has been entered on the diary card

Bleeding/spotting-free One or more consecutive days on which no bleeding or

interval spotting has been entered on the diary card

Bleeding/spotting One bleeding/spotting episode and the immediately

segment following bleeding/spotting-free interval

Reference period The number of consecutive days upon which the analysis
is based (usually taken as 90 days for women using long-
acting hormonal systems, and 28 or 30 days for women
using once-a-month systems, including combined oral
contraception)

Different types of Number of bleeding/spotting days

analysis, which can be Number of bleeding/spotting episodes
undertaken on bleeding Mean, range of lengths of bleeding/spotting episodes (or
patterns within a medians and centiles for box-whisker plot analysis)
reference period
Mean, range (medians and centiles) of lengths of
bleeding/spotting-free intervals
Number of spotting days and spotting-only episodes

Data from: Fraser IS. Bleeding arising from the use of exogenous steroids. Baillieres Best Pract Res Clin
Obstet Gynaecol 1999; 13:203.

Graphic 103240 Version 1.0

PALM-COEIN classification system for abnormal uterine
bleeding in nongravid reproductive-age women

Basic classification system. The basic system comprises four categories that
are defined by visually objective structural criteria (PALM: polyp,
adenomyosis, leiomyoma, and malignancy and hyperplasia), four that are
unrelated to structural anomalies (COEI: coagulopathy, ovulatory
dysfunction, endometrial, iatrogenic), and one reserved for entities that are
not otherwise classified (N). The leiomyoma category (L) is subdivided into
patients with at least one submucous myoma (L SM ) and those with
myomas that do not impact the endometrial cavity (L O ). In the 2018
version, the words "submucosal" and "other" do not appear and the phrase
"not yet classified" has been changed to "not otherwise classified."

Reproduced from: Munro MG, Critchley HO, Broder MS, Fraser IS, FIGO Working Group on
Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine
bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet 2011; 113:3.
Illustration used with the permission of Elsevier Inc. All rights reserved.
Legend updated from: Munro MG, Critchley HO, Fraser IS for the FIGO Menstrual Disorders
Committee. The two FIGO systems for normal and abnormal uterine bleeding symptoms and
classification of causes of abnormal uterine bleeding in the reproductive years: 2018
revisions. Int J Gynaecol Obstet 2018; 145:393.

Graphic 90483 Version 3.0

Questions to ask to help quantify blood loss during menses

How often do you change your sanitary pad/tampon during peak flow days?

How many pads/tampons do you use over a single menstrual period?

Do you need to change the pad/tampon during the night?

How large are any clots that are passed?

Has a medical provider told you that you are anemic?

Women with a normal volume of menstrual blood loss tend to:

Change pads/tampons at ≥3 hour intervals

Use fewer than 21 pads/tampons per cycle

Seldom need to change the pad/tampon during the night

Have clots less than 1 inch in diameter

Not be anemic

Adapted from: Warner PE, Critchley HD, Lumsden MA, et al. Menorrhagia I: Measured blood loss, clinical
features, and outcome in women with heavy periods: A survey with follow-up data. Am J Obstet Gynecol
2004; 190:1216.

Graphic 69390 Version 3.0

Risk factors for endometrial cancer

Relative risk (RR)

Risk factor (other statistics are noted when
used)

Increasing age 1 to 2% cumulative incidence of

endometrial cancer in females age 50 to
70 years

Unopposed estrogen therapy 2 to 10

Tamoxifen therapy 2

Early menarche NA

Late menopause (after age 55) 2

Nulliparity 2

Polycystic ovary syndrome (chronic 3

anovulation)

Obesity For type I endometrial cancer: OR 1.5 for

overweight (BMI 25.0 to <30 kg/m 2 ), 2.5
for class 1 obesity (30.0 to <35 kg/m 2 ), 4.5
for class 2 obesity (35.0 to 39.9 kg/m 2 ),
and 7.1 for class 3 obesity (≥40.0 kg/m 2 ).

For type II: OR 1.2 for overweight (BMI

25.0 to <30 kg/m 2 ), 1.7 for class 1 obesity
(30.0 to <35 kg/m 2 ), 2.2 for class 2 obesity
(35.0 to 39.9 kg/m 2 ), and 3.1 for class 3
obesity (≥40.0 kg/m 2 ).

Diabetes mellitus 2

Estrogen-secreting tumor NA

Lynch syndrome (hereditary nonpolyposis 13 to 71% lifetime risk

colorectal cancer)

Cowden syndrome 13 to 28% lifetime risk

Family history of endometrial, ovarian, NA

breast, or colon cancer

NA: RR not available; OR: odds ratio; BMI: body mass index.
Data from:
1. Heald B, Mester J, Rybicki L, et al. Frequent gastrointestinal polyps and colorectal adenocarcinomas in
a prospective series of PTEN mutation carriers. Gastroenterology 2010; 139:1927.
2. Pilarski R, Stephens JA, Noss R, et al. Predicting PTEN mutations: an evaluation of Cowden syndrome
and Bannayan-Riley-Ruvalcaba syndrome clinical features. J Med Genet 2011; 48:505.
3. Ramsoekh D, Wagner A, van Leerdam ME, et al. Cancer risk in MLH1, MSH2 and MSH6 mutation
carriers; different risk profiles may influence clinical management. Hered Cancer Clin Pract 2009;
7:17.
4. Riegert-Johnson DL, Gleeson FC, Roberts M, et al. Cancer and Lhermitte-Duclos disease are common in
Cowden syndrome patients. Hered Cancer Clin Pract 2010; 8:6.
5. Setiawan VW, Yang HP, Pike MC, et al. Type I and II endometrial cancers: have they different risk
factors? J Clin Oncol 2013; 31:2607.
6. Smith RA, von Eschenbach AC, Wender R, et al. American Cancer Society guidelines for the early
detection of cancer: Update of early detection guidelines for prostate, colorectal, and endometrial
cancers. CA Cancer J Clin 2001; 51:38.
7. Tan MH, Mester JL, Ngeow J, et al. Lifetime cancer risks in individuals with germline PTEN mutations.
Clin Cancer Res 2012; 18:400.
8. Ten Broeke SW, van der Klift HM, Tops CMJ, et al. Cancer risks for PMS2-associated Lynch syndrome. J
Clin Oncol 2018; 36:2961.

Graphic 62089 Version 18.0

Medications that cause hyperprolactinemia

Frequency of prolactin
Medication class Mechanism
elevation*

Antipsychotics, first generation

Chlorpromazine Moderate Dopamine D 2 receptor
blockade within
Fluphenazine High
hypothalamic
Haloperidol High tuberoinfundibular system.
Loxapine Moderate

Perphenazine Moderate

Pimozide Moderate

Thiothixene Moderate

Trifluoperazine Moderate

Antipsychotics, second generation

Aripiprazole None or low Dopamine D 2 receptor
blockade.
Asenapine Moderate

Clozapine None or low

Iloperidone None or low

Lurasidone None or low

Olanzapine Low

Paliperidone High

Quetiapine None or low

Risperidone High

Ziprasidone Low

Antidepressants, cyclic
Amitriptyline Low Not well understood.
Possibly by GABA
Desipramine Low
stimulation and indirect
Clomipramine High modulation of prolactin
Nortriptyline None release by serotonin.
 Antidepressants, SSRI

Citalopram, fluoxetine, None or low (rare reports) Same as for cyclic

fluvoxamine, paroxetine, antidepressants.
sertraline

Antidepressants, other

Bupropion, venlafaxine, None Not applicable.

mirtazapine,
nefazodone, trazodone

Antiemetic and gastrointestinal

Metoclopramide High Dopamine D 2 receptor

blockade.
Domperidone (not High
available in United
States)

Prochlorperazine Low

Antihypertensives

Verapamil Low Not well understood.

Specific to verapamil. May
involve calcium influx
inhibition within
tuberoinfundibular
dopaminergic neurons.

Methyldopa Moderate Decreased conversion of L-

dopa to dopamine;
suppression of dopamine
synthesis.

Most other None Not applicable.

antihypertensives
(including other calcium
channel blockers)

Opioid analgesics
Methadone, morphine, Transient increase for Potentially an indirect
others several hours following effect of mu opiate
dose receptor activation.

Medication-induced hyperprolactinemia can cause decreased libido and erectile

dysfunction in males and galactorrhea and amenorrhea in females.
GABA: gamma-aminobutyric acid; SSRI: selective serotonin reuptake inhibitor.

* Frequency of increase to abnormal prolactin levels with chronic use: high: >50%;
moderate: 25 to 50%; low: <25%; none or low: case reports. Effect may be dose
dependent.

Data from:
1. Molitch ME. Drugs and prolactin. Pituitary 2008; 11:209.
2. Molitch ME. Medication induced hyperprolactinemia. Mayo Clin Proc 2005; 80:1050.
3. Coker F, Taylor D. Antidepressant-induced hyperprolactinaemia: incidence, mechanisms and
management. CNS Drugs 2010; 24:563.
4. Drugs for psychiatric disorders. Treat Guidel Med Lett 2013; 11:53.

Graphic 75914 Version 13.0

Screening for bleeding disorders in women with heavy menstrual
bleeding

Initial screening for an underlying disorder of hemostasis in patients

with excessive menstrual bleeding should be structured by medical
history (positive screen comprises any of the following):*
Heavy menstrual bleeding since menarche

One of the following:

Postpartum hemorrhage

Surgery-related bleeding

Bleeding associated with dental work

Two or more of the following symptoms:

Bruising one to two times per month

Epistaxis one to two times per month

Frequent gum bleeding

Family history of bleeding symptoms

* Patients with a positive screen should be considered for further evaluation, including
consultation with a hematologist and testing of von Willebrand factor and ristocetin
cofactor.

Original figure modified for this publication. Kouides PA, Conard J, Peyvandi F, et al. Hemostasis and
menstruation: appropriate investigation for underlying disorders of hemostasis in women with excessive
menstrual bleeding. Fertil Steril 2005; 84:1345. Table used with the permission of Elsevier Inc. All rights
reserved.

Graphic 90289 Version 2.0

Evaluation and differential diagnosis of abnormal uterine
bleeding (AUB) in nonpregnant reproductive-age women

Other Differential diagnosis

Bleeding associated
Less Evaluation
pattern clinical Common
common
features etiologies
etiologies
Regular Enlarged Uterine leiomyoma   - Pelvic
menses that uterus on ultrasound
are heavy or examination,
- Saline
prolonged discrete
infusion
masses may
sonography
be noted
or
hysteroscopy
(if
intracavitary
pathology is
suspected)

- Adenomyosis   Pelvic
Dysmenorrhea ultrasound

- Enlarged,
boggy uterus
on
examination

- Family Bleeding disorder   Testing for

history of bleeding
bleeding disorder
disorder

- Symptoms of
bleeding
diathesis

-
Anticoagulant
therapy

Risk factors for   Endometrial Endometrial

uterine carcinoma or sampling
malignancy uterine
 sarcoma

Regular   Endometrial polyp   - Pelvic

menses with ultrasound
intermenstrual
- Saline
bleeding
infusion
sonography
or
hysteroscopy
(if available)

Risk factors for   Endometrial Endometrial

uterine carcinoma or sampling
malignancy uterine
sarcoma

Recent history   Chronic Endometrial

of uterine or endometritis sampling
cervical
procedure or
childbirth,
particularly if
infection was
present

Irregular   Ovulatory    
bleeding, may dysfunction:
be more or
Hirsutism, PCOS   Total
less frequent
acne, and/or testosterone
than normal
obesity and/or other
menses and
androgens
volume and
(may not be
duration may
increased in
vary
all women
with PCOS)

Galactorrhea Hyperprolactinemia   Prolactin

- Recent Thyroid disease   Thyroid

weight gain or function tests
loss

- Heat or cold
intolerance

- Family
history of
 thyroid
dysfunction

Risk factors for   Endometrial  Endometrial

uterine carcinoma or sampling
malignancy uterine
sarcoma

Secondary History of Ovulatory   Refer to

amenorrhea irregular dysfunction ovulatory
bleeding dysfunction
above

Poor nutrition Hypothalamic   - Follicle-

or intense amenorrhea stimulating
exercise hormone
- Luteinizing
hormone

- Estradiol

Hot flushes Premature ovarian   Follicle-

insufficiency stimulating
hormone

Recent history   Cervical On pelvic

of uterine or stenosis examination,
cervical instrument
procedure or cannot be
childbirth, passed
particularly if through
infection was internal
present cervical os
(menses may
  Intrauterine Hysteroscopy
present, but
adhesions
abnormally
(Asherman
light or brief)
syndrome)

Irregular or   Iatrogenic AUB    

heavy bleeding
in a
patient using
hormonal
contraceptives
or with an
intrauterine
 device

Other uncommon etiologies of AUB include a uterine arteriovenous malformation or

endometriosis.

PCOS: polycystic ovarian syndrome.

Graphic 90595 Version 5.0

Causes of heavy or prolonged menses

Coagulopathy Structural lesion

von Willebrand disease Uterine leiomyomas (fibroids)

Thrombocytopenia (due to idiopathic Adenomyosis

thrombocytopenic purpura,
Endometrial polyps
hypersplenism, chronic renal failure)
Other
Acute leukemia
Endometritis
Anticoagulants
Hypothyroidism
Advanced liver disease
Intrauterine device
Neoplasm
Hyperestrogenism
Endometrial hyperplasia or carcinoma
Endometriosis
Uterine sarcoma

Graphic 55437 Version 4.0

Patients who should undergo evaluation for endometrial
hyperplasia or endometrial cancer

Abnormal uterine bleeding

Postmenopausal patients – Any uterine bleeding, regardless of volume (including

spotting or staining). Pelvic ultrasound to evaluate endometrial thickness is an
alternative to endometrial sampling in appropriately selected patients. A
thickened endometrium should be further evaluated with endometrial sampling.

Age 45 years to menopause – In any patient, bleeding that is frequent (interval

between the onset of bleeding episodes is <21 days), heavy, or prolonged (>8
days). In patients who are ovulatory, this includes intermenstrual bleeding.

Younger than 45 years – Any abnormal uterine bleeding in patients with BMI ≥30
kg/m 2 . In patients with BMI <30 kg/m 2 , abnormal uterine bleeding that is
persistent and occurs in the setting of one of the following: chronic ovulatory
dysfunction, other exposure to estrogen unopposed by progesterone, failed
medical management of the bleeding, or patients at high risk of endometrial
cancer (eg, Lynch syndrome, Cowden syndrome).

In addition, endometrial neoplasia should be suspected in premenopausal

patients who are anovulatory and have prolonged periods of amenorrhea (six or
more months).

Cervical cytology results

Presence of AGC-endometrial.

Presence of AGC-all subcategories other than endometrial – If ≥35 years of age or

at risk for endometrial cancer (risk factors or symptoms).

Presence of benign-appearing endometrial cells in patients ≥40 years of age who

also have abnormal uterine bleeding or risk factors for endometrial cancer.

Other indications

Monitoring of patients with endometrial pathology (eg, endometrial hyperplasia).

Screening in patients at high risk of endometrial cancer (eg, Lynch syndrome).

These recommendations are based on an average age of menopause of 51 years.

Evaluation of patients who undergo menopause earlier should be individualized based
on gynecologic history and risk of endometrial neoplasia.
BMI: body mass index; AGC: atypical glandular cells.

Graphic 58600 Version 15.0

Causes of intermenstrual bleeding

Drugs
Oral contraceptives

Infection
Cervicitis*

Endometritis

Sexually transmitted ulcerations*

Vaginitis

Benign growths
Cervical polyps*

Endometrial polyps

Ectropion*

Uterine fibroids

Vulvar skin tags, sebaceous cysts, condylomata

Vaginal Gartner's duct cysts, polyps, adenosis

Cancer
Uterine

Cervical*

Vaginal

Vulvar

Rarely ovarian or fallopian tube

Trauma
Previous cesarean delivery (ie, cesarean scar defect)

* Often cause postcoital bleeding.

Graphic 67618 Version 2.0

Causes of ovulatory dysfunction

Primary hypothalamic-pituitary dysfunction

Immaturity at onset of menarche or perimenopausal decline

Intense exercise

Eating disorders

Stress

Idiopathic hypogonadotropic hypogonadism

Hyperprolactinemia

Lactational amenorrhea

Pituitary adenoma or other pituitary tumors

Kallman syndrome

Tumors, trauma, or radiation of the hypothalamic or pituitary area

Sheehan's syndrome

Empty sella syndrome

Lymphocytic hypophysitis (autoimmune diseases)

Other disorders
Polycystic ovary syndrome

Hyperthyroidism or hypothyroidism

Hormone-producing tumors (adrenal, ovarian)

Chronic liver or renal disease

Cushing's disease

Congenital adrenal hyperplasia

Premature ovarian failure, which may be autoimmune, genetic, surgical idiopathic, or

related to drugs or radiation

Turner syndrome

Androgen insensitivity syndrome

Medications
Estrogen-progestin contraceptives
 Progestins

Antidepressant and antipsychotic drugs

Corticosteroids

Chemotherapeutic agents

Graphic 79628 Version 6.0

Sonohysterogram of endometrial polyp

Sonohysterograms of two patients, both with an endometrial polyp; Doppler shows flow to the polyp vi

Courtesy of Andrew M Kaunitz, MD.

Graphic 131945 Version 2.0

Saline infusion sonohysterogram of a submucous
myoma

A posterior mid-segment submucous myoma measuring 1.6 x 1.9

cm is identified after infusion of saline. The distance from the back
of the myoma to the serosal surface measures 1.2 cm (calipers). The
endometrium surrounding the fluid is thin, compatible with early
proliferative phase.

Courtesy of Steven Goldstein, MD.

Graphic 50777 Version 4.0

Fibroid locations in the uterus

These figures depict the various types and locations of fibroids. An individual may have one or
more types of fibroids.

Graphic 53241 Version 6.0

PALM-COEIN subclassification system for leiomyomas

FIGO leiomyoma subclassification system. System 2 classification system including the FIGO leiomyoma
subclassification system. The system that includes the tertiary classification of leiomyomas categorizes
submucous group according to the original Wamsteker et al system [1] and adds categorizations for int
subserosal, and transmural lesions. Intracavitary lesions are attached to the endometrium by a narrow
(≤10% or the mean of three diameters of the leiomyoma) and are classified as Type 0, whereas Types 1
require a portion of the lesion to be intramural: with Type 1 being less than 50% of the mean diameter
at least 50%. Type 3 lesions are totally intramural but also about the endometrium. Type 3 are formally
distinguished from Type 2 with hysteroscopy using the lowest possible intrauterine pressure necessary
visualization. Type 4 lesions are intramural leiomyomas that are entirely within the myometrium, with n
extension to the endometrial surface or to the serosa. Subserous (Types 5, 6, and 7) leiomyomas repres
mirror image of the submucous leiomyomas: with Type 5 being at least 50% intramural, Type 6 being le
50% intramural, and Type 7 being attached to the serosa by a stalk that is also ≤10% or the mean of thr
diameters of the leiomyoma. Classification of lesions that are transmural are categorized by their relati
both the endometrial and the serosal surfaces. The endometrial relationship is noted first, with the sero
relationship second (eg, Type 2-5). An additional category, Type 8, is reserved for leiomyomas that do n
to the myometrium at all, and would include cervical lesions (demonstrated), those that exist in the rou
broad ligaments without direct attachment to the uterus, and other so-called "parasitic" lesions.

FIGO: International Federation of Gynecology and Obstetrics.

Reference:
1. Wamsteker K, Emanuel MH, de Kruif JH. Transcervical hysteroscopic resection of submucous fibroids for abnormal uterine
Results regarding the degree of intramural extension. Obstet Gynecol 1993; 82:736.
From: Munro MG. Abnormal Uterine Bleeding. Cambridge: Cambridge University Press, 2010. Copyright © 2010 M. Munro. Rep
the permission of Cambridge University Press.
Updated with information from: Munro MG, Critchley HOD, Fraser IS, FIGO Menstrual Disorders Committee. The two FIGO system
normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive
revisions. In J Gynaecol Obstet 2018; 143:393.

Graphic 91085 Version 3.0

Saline infusion sonography of a patient with
uterine bleeding

Saline infusion sonography of a patient with uterine bleeding

reveals fluffy endometrial tissue occupying the right lateral half of
the endometrial cavity while the left side is thin.

Courtesy of Steven Goldstein, MD.

Graphic 60457 Version 3.0

Contributor Disclosures
Andrew M Kaunitz, MD Grant/Research/Clinical Trial Support: AbbVie [Polycystic ovary
syndrome];Bayer[Treatment of menopausal symptoms];Exeltis[Oral
contraception];Medicines360 [Heavy menstrual bleeding];Merck [Contraceptive
implant];Mithra[Treatment of menopausal symptoms]. All of the relevant financial relationships
listed have been mitigated. Robert L Barbieri, MD No relevant financial relationship(s) with
ineligible companies to disclose. Deborah Levine, MD No relevant financial relationship(s) with
ineligible companies to disclose. Alana Chakrabarti, MD No relevant financial relationship(s)
with ineligible companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found,
these are addressed by vetting through a multi-level review process, and through requirements
for references to be provided to support the content. Appropriately referenced content is
required of all authors and must conform to UpToDate standards of evidence.

Conflict of interest policy